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Research Article

HEPATIC STEM CELLS: A REVIEW

Carina J. Vessey, Pauline de la M. Hall Department of Anatomical Pathology, University of Cape Town, South Africa
Pages 130-141 | Published online: 06 Jul 2009

  • Sell S. Is there a liver stem cell? Cancer Rex 1990: 50: 3811-15.
  • Thorgeirsson SS. Hepatic stem cells in liver regeneration. FASEB J 1996: 10: 1249-56.
  • Grisham JW, Thorgeirsson SS. Liver stem cells. In: Stem cells. Potten CS, editor. New York: Academic Press, 1997: 233-82.
  • Golding M, Sarraf C, Lalani E-N, Alison M. Reactive biliary epithelium: The product of a pluripotential stem cell compartment? Hum Pdtlwl 1996: 27: 872-84.
  • Potten CS, Loeffler M. Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Development 1990: 110: 1001-20.
  • Marceau N. Cell lineages and differentiation programs in epidermal, urothelial and hepatic tissues and their neoplasms. Lab Invest 1990: 63: 4-20.
  • Wright N, Alison M. The Biology if Epithelial Populations. VoI 2. Oxford: Clarendon Press, 1984: 873-980.
  • Alison MR. Regulation of liver growth. Physiol Rev 1986: 66: 499-541.
  • Rhim JA, Sandgren EP, Degen JE, Palmiter RD, Brinster RE. Replacement of diseased mouse liver by hepatic cell transplantation. Science 1994: 263: 1149-52.
  • Moore KE. The Developing Human: Clinically Oriented Embryology. 3rd ed. London: WB Saunders Co, 1982: 233-4.
  • Shiojiri N, Lemire JM, Fausto N. Cell lineages and oval cell progenitors in rat liver development. Cancer Rex 1991: 51: 2611-20.
  • Zajicek G, Oren R, Weinreb M. The streaming liver. Liver 1985: 5: 293-300.
  • Bralet MR Branchereau S, Brechot C, Ferry N. Cell lineage study in the liver using retroviral mediated gene transfer. Evidence against the streaming of hepatocytes in normal liver. Am J Pathol 1994: 144: 896-905.
  • Kennedy S, Rettinger S, Flye MW, Parker Ponder K. Experiments in transgenic mice show that hepatocytes are the source for postnatal liver growth and do not stream. Hepatoloxy 1995: 22: 160-8.
  • Kinosita R. Studies on the carcinogenic chemical substances. Trans Soc Patlwl Jpn 1937: 27: 665-727.
  • Wilson JW, Leduc EH. Role of cholangioles in restoration of the liver of the mouse after dietary injury. J Pathol Bacterial 1958: 76: 441-9.
  • SoIt DB, Medline A, Farber E. Rapid emergence of carcinogen induced lesions in a new model for the sequential analysis of liver carcinogenesis. Am J Pathol 1977: 88: 595-609.
  • Rodgers AE. Variable effects of a lipotrope deficient high fat diet on chemical carcinogenesis in rats. Cancer Res 1975: 35: 2469-75.
  • Sell S, Osborn K, Leffert HL. Autoradiography of "oval cells" appearing rapidly in the livers of rats fed N-2-fluorenylacetamide in a choline devoid diet. Carcinogenesis 1981: 2: 7-14.
  • Lemmer ER, Hall P de la M, Omori N, et al. Histopathology and gene expression changes in rat liver during feeding of fumonisin B 1, a carcinogenic mycotoxin produced by Fusarium moniliforme. CarcinoKenexix 1999: 20: 817-24.
  • Farber E. Similarities in the sequence of early histologie changes induced in the livers of rats by ethionine, 2-acetylaminoazobenzene and 3'-methyl-4-dimethylaminoazobenzene. Cancer Res 1956: 16: 142-8.
  • Sarraf C, Lalani E, Golding M, Anilkumar TV, Poulsom R, Alison M. Oval cell activation in the rat liver. Am J Pathol 1994: 145: 1114-26.
  • Van Eyken P, De Vos R, Desmet VJ. Progenitor ("stem") cells in alcoholic liver disease? In: Hall P, editor. Alcoholic liver disease: Pathotogy and pathogenesis, 2nd ed. London: Edward Arnold, 1995: 160-71.
  • Dunsford HA, Maset R, Salmon J, Sell S. Connection of duct-like structures induced by chemical hepatocarcinogen to portal bile ducts in the rat liver detected by injection of bile ducts with a pigmented barium gelatin medium. Am J Pathol 1985: 118: 218-24.
  • Makino Y, Yamamoto K, Tsuji T. Three dimensional arrangement of ductular structures formed by oval cells during hepatocarcinogenesis. Acta Med Okayama 1988:42: 143-50.
  • Lenzi R, Liu MH, Slott PA, et al. Histogenesis of bile duct-like cells proliferating during ethionine hepatocarcinogenesis. Evidence for a biliary epithelial nature of oval cells. Lab Invest 1992: 66: 390-402.
  • Novikoff PM, Yam A, Oikawa I. Blast-like cell compartment in carcinogen-induced proliferating bile ductules. Am J Pathol 1996: 148: 1473-92.
  • LeMire JM, Shiojiri N, Fausto N. Oval cell proliferation and the origin of small hepatocytes in liver injury induced by D-galactosamine. Am J Pathol 1991: 139: 535-52.
  • Dunsford HA, Sell S. Production of monoclonal antibodies to preneoplastic liver cell populations induced by chemical carcinogens in rats and to transplantable Morris hepatomas. Cancer Res 1989: 49: 4887-93.
  • Bisgaard HC, Parmelee DC, Dunsford HA, Sechi S, Thorgeirsson SS. Keratin 14 protein in cultured nonparenchymal rat hepatic epithelial cells: characterization of keratin 14 and keratin 19 as antigens for the commonly used mouse monoclonal antibody OV-6. Mol Carcinogen 1993: 7: 60-6.
  • Tee LB, Kirilak Y, Huang WH, Smith PG, Morgan RH, Yeoh GC. Dual phenotypic expression of hepatocyte and bile ductular markers in developing and preneoplastic rat liver. Carcinogenesis 1996: 17: 251-9.
  • Dabeva MD, Shafritz DA. Activation, proliferation, and differentiation of progenitor cells into hepatocytes in the D-galactosamine model of liver regeneration. Am J Pathol 1993: 143: 1606-20.
  • Golding M, Sarraf C, Lalani E-N, et at. Oval cell differentiation into hepatocytes in the acetylaminofluorene-treated regenerating rat liver. Hepatology 1995: 22: 1243-53.
  • Bisgaard HC, Nagy R Ton PT, Hu Z, Thorgeirsson SS. Modulation of keratin 14 and a-fetoprotein expression during hepatic oval cell proliferation and liver regeneration. J Cell Physiol 1994: 159: 475-84.
  • Sirica AE, Cihla HP. Isolation and partial characterizations of oval and hyperplastic bile ductular cell-enriched populations from the livers ot carcinogen and noncarcinogen-treated rats. Cancer Res 1984: 44: 3454-66.
  • Haruna Y, Saito K, Spaulding S, Nalesnik MA, Gerber MA. Identification of bipotential progenitor cells in human liver development. Heptitoloxy 1996: 23: 476-81.
  • Sell S, Leffert HL. An evaluation of cellular lineages in the pathogenesis of experimental hepatocellular carcinoma. Hepatology 1982: 2: 77-87.
  • Haque S, Haruna Y, Saito K, et al. Identification of bipotential progenitor cells in human liver regeneration. Lab Invest 1996: 75: 699-705.
  • Demetris AJ, Seaberg EC, Wennenberg A, Ionellie J, Michalopoulos G. Ductular reaction after submassive necrosis in humans. Special emphasis on analysis of ductular hepatocytes. Am J Pathol 1996: 149: 439-48.
  • Grisham JW. Cell types in long-term propagable cultures of rat liver. Ami N Y Acail Sd 1980: 349: 128-37.
  • Lazaro CA, Rhim JA, Yamada Y, Fausto N. Generation of hepatocytes from oval cell precursors in culture. Cancer Res 1998: 58: 5514-22.
  • Yasui O, Miura N, Terada K, Kawarada Y, Koyama K, Sugiyama T. Isolation of oval cells from Long-Evans Cinnamon rats and their transformation into hepatocytes in vim in the rat liver. Hepatology 1997: 25: 329-34.
  • Tee LB, Kirilak Y, Huang WH, Morgan RH, Yeoh GC. Differentiation of oval cells into duct-like cells in preneoplastic liver of rats placed on a choline-deficient diet supplemented with ethionine. CarcinoKenesis 1994: 15: 2747-56.
  • Evarts RP, Hu Z, Oniori N, Marsden ER, Thorgeirsson SS. Precursorproduct relationship between oval cells and hepatocytes: comparison between tritiated thymidine and bromodeoxyuridine as tracers. Carcinogenesis 1996: 17: 2143-51.
  • Tsao M-S, Smith JD, Nelson KG, Grisham JW. A diploid epithelial cell line from the normal adult rat liver with the phenotypic properties of "oval" cells. Exp Cell Res 1984: 154: 38-52.
  • Paris RA, Hixson DC. Selective proliferation of chemically altered rat liver epithelial cells following hepatic transplantation. Transplantation 1989: 48: 87-92.
  • Coleman WB, Wennerberg AE, Smith GJ, Grisham JW. Regulation of the differentiation of diploid and some aneuploid rat liver epithelial (stem-like) cells by the hepatic microenvironment. Am J Ptithol 1993: 142: 1373-82.
  • Petersen BE, Zajac VF, Michalopoulos GK. Hepatic oval cell activation in response to injury following chemically induced periportal or pericentral damage in rats. Hepatology 1998: 27: 1030-8.
  • Crosby AH, Hubscher S, Fabris L, et til. Immunolocalization of putative human liver progenitor cells in livers from patients with end-stage primary biliary cirrhosis and sclerosing cholangitis using the monoclonal antibody OV-6. Am J Pathol 1998: 152: 771-9.
  • Roskams T, De Vos R, Van Eyken R Myazaki H, Van Damme B, Desmet V Hepatic OV-6 expression in human liver disease and rat experiments: evidence for hepatic progenitor cells in man. J Hepatol 1998: 29: 455-63.
  • Popper H. The relation of mesenchymal cell products to hepatic epithelial cell systems. Prof· Liver Dix 1990: 9: 27-38.
  • Gerber MA, Thung SN, Shen S, Stromeyer FW, Ishek KG. Phenotypic characterization of hepatic proliferation. Antigenic expression by proliferating epithelial cells in fetal liver, massive hepatic necrosis, and nodular transformation of the liver. Am J Pathol 1983: 110: 70-4.
  • Desmet V, Roskams T, Van Eyken P. Ductular reaction in the liver. Ptithol Rex Pmct 1995: 191: 513-24.
  • Sirica AE. "Ductular hepatocytes". Histot Hixtoptithol 1995: 10: 433-56.
  • De Vos R, Desmet V. Ultrastructural characteristics of novel epithelial cell types identified in human pathologic liver specimens with chronic ductular reaction. Am J Pathol 1992: 140: 1441-50.
  • Roskams T, van den Oord JJ, De Vos R, Desmet VJ. Neuroendocrine features of reactive bile ductules in cholestatic liver disease. Am J Pathol 1990: 137: 1019-25.
  • Roskams T, Campos RV, Drucker DJ, Desmet VJ. Reactive human bile ductules express parathyroid hormone-related peptide. Hixtoptithology 1993: 23: 11-19.
  • Crosby HC, Baumann W, Kelly WA, Strain AJ. Isolation and growth in vitro of human liver epithelial cells with progenitor (stem) cell properties. Hepatology 1998: 28: 522A.
  • Roskams T, De Vos R, Desmet V. "Undifferentiated progenitor cells" in focal nodular hyperplasia of the liver. Histopathology 1996: 28: 291-9.
  • Smith PG, Tee LB, Yeoh GC. Appearance of oval cells in the liver of rats after long-term exposure to ethanol. Hepatology 1996: 23: 145-54.
  • Ray MB. Distribution patterns of cytokeratin antigen determinants in alcoholic and non-alcoholic liver diseases. Hum Pathol 1987: 18: 61-6.
  • Ray MB, Mendenhall CL, French SW, Gartside PS. Bile duct changes in alcoholic liver disease. Liver 1993: 13: 36-45.
  • Lai Y-S, Thung S, Gerber M, Chen M-L, Schaffner F. Expression of cytokeratins in normal and diseased livers and in primary liver carcinomas. Arch Pathol Lab Med 1989: 113: 134-8.
  • Hall de La M P. Alcoholic liver disease. In: MacSween RNM, Anthony PP, Scheuer PJ, Burt AD, Portman BC, editors. Pathology of the liver. 4th ed. Edinburgh: Churchill Livingstone, 2000: Chapter 6.
  • Hsia CC, Evarts RP, Nakatsukasa H, Marsden ER, Thorgeirsson SS. Occurrence of oval-type cells in hepatitis B virus-associated human hepatocarcinogenesis. Hepatotogy 1992: 16: 1327-33.
  • Hsia CC, Thorgeirsson SS, Tabor E. Expression of hepatitis B surface and core antigens and transforming growth factor-alpha in "oval cells" of the liver in patients with hepatocellular carcinoma. J Med Virol 1994: 43: 216-21.
  • Lowes KN, Brennan BA, Yeoh, GC, Olynyk JK. Oval cell numbers in human chronic liver diseases are directly related to disease severity. Am J Pathol 1999: 154: 537-41.
  • Ruck P, Xiao JC, Pietsch T, Von Schweinitz D, Kaiserling E. Hepatic stem-like cells in hepatohlastoma: expression of cytokeratin 7, albumin and oval cell associated antigens detected by OV-1 and OV6. Histopathology 1997: 31: 324-9.
  • Ruck P, Xiao JC, Kaiserling E. Small epithelial cells and the histogenesis of hepatoblastoma. Am J Pathol 1996: 148: 321-9.
  • Abenoza P, Manivel JC, Wick MR, Hagen K, Dehner LP. Hepatoblastoma: an immunohistochemical and ultrastructural study. Hum Pathol 1987: 18: 1025-35.
  • Sell S. The role of determined stem-cells in the cellular lineage of hepatocellular carcinoma. Int J Der Biol 1993: 37: 189-201.
  • Potter VR. Phenotypic diversity in experimental hepatomas: the concept of blocked ontogeny. Br J Cancer 1978: 38: 1-23.
  • Goodman ZD, Ishak KG, Langloss JM, Sesterhenn IA, Rabin L. Combined hepatocellular-cholangiocellular carcinoma. Cancer 1985: 55: 124-35.
  • Wanless IR, Callea F, Craig JR, et al. International Working Party: Terminology of nodular hepatocellular lesions. Hepatology 1995: 22: 983-93.
  • Ferrel LD, Crawford JM, Dhillon AP, Scheuer PJ, Nakanuma Y. Proposal for standardized criteria for the diagnosis of benign, borderline, and malignant hepatocellular lesions arising in chronic advanced liver disease. Am J Surg Pathol 1993: 17: 1113-23.
  • Teebor GW, Becker FF. Regression and persistence of hyperplastic hepatic nodules induced by N-2-fluorenylacetamide and their relationship to hepatocarcinogenesis. Cancer Rex 1971: 31: 1-3.
  • Sell S, Dunsford HA. Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma. Am J Pathol 1989: 134: 1347-63.
  • Tatematsu M, Kaku T, Medline A, Farber E. Intestinal metaplasia as a common option of oval cells in relation to cholangiofibrosis in liver of rats exposed to 2-acetylaminofluorene. Lab Invest 1985: 52: 354-62.
  • Anilkumar TV, Golding M, Edwards RJ, Lalani E-N, Sarraf CE. Alison MR. The resistant hepatocyte model of carcinogenesis in the rat: the apparent independent development of oval cell proliferation and early nodules. Carcinogenexix 1995: 16: 845-53.
  • Paris RA, Monfils BA, Dunsford HA, Hixson DC. Antigenic relationship between oval cells and a subpopulation of hepatic foci, nodules and carcinomas induced by the "resistant hepatocyte" model system. Cancer Rex 1991: 51: 1308-17.
  • Tsao MS, Grisham JW. Hepatocarcinomas, cholangiocarcinomas and hepatoblastomas produced by chemically transformed rat liver epithelial cells: A light and electron microscopic analysis. Am J Pathol 1987: 127: 168-81.
  • Yaswen P, Hayner NT, Fausto N. Isolation of oval cells by centrifugal elutriation and comparison with other cell types purified from normal and preneoplastic livers. Cancer Rex 1984: 44: 324-31.
  • Sirica AE, Mathis GA, Sano N, Elmore LW. Isolation, culture, and transplantation of intrahepatic biliary epithelial and oval cells. Pathobiology 1990: 58: 44-64.
  • Park R, Heck DR, Dienes HR Oesch F, Steinberg P. Isolation, biochemical characterization, long-term culture, and phenotype modulation of oval cells from carcinogen fed rats. Exp Cell Rex 1993: 204: 198-209.
  • Dagli M, Guerra JL, Sinhorini IL, et al. Beta-carotene reduces the ductular (oval) cell reaction in the liver of Wistar rats submitted to the resistant hepatocyte model of carcinogenesis. Pathology 1998: 30: 259-66.
  • Nagy P Kiss A, Schnur J, Thorgeirsson SS. Dexamethasone inhibits the proliferation of hepatocytes and oval cells but not bile ducts in rat liver. Hepatology 1998: 28: 423-9.
  • Anilkumar T, Ryan CJ, Aslam M, Poulsom R, Alison M. The antiproliferative effect of plasma from rats with acute fulminant hepatic failure. Scaml J Gaxtmenteml 1997: 32: 1152-61.
  • Henne-Bruns D, Kruger U, Sumpelmann D, Lierse W, Kremer B. Intraperitoneal hepatocyte transplantation: morphological results. Virchows Arch A Pathol Anal Hixtopathol 1991: 419: 45-50.
  • Hillan K, Burt AD, George WD, MacSween RN, Griffiths MR, Bradley JA. Intrasplenic hepatocyte transplantation in rats with experimental liver injury: morphological and morphometric studies. J Pathol 1989: 159: 67-73.
  • Nordlinger B, Wang SR, Bouma ME, et al. Can hepatocytes proliferate when transplanted into the spleen? Demonstration by autohistoradiography in the rat. Eur Surg Res 1987: 19: 381-7.
  • Ponder KP, Gupta S, Leland F, et til. Mouse hepatocytes migrate to liver parenchyma and function indefinitely after intrasplenic transplantation. Proc Natl Acad Sd USA 1991: 88: 1217-21.
  • Strom SC, Fisher RA, Thompson MT, et cil. Hepatocyte transplantation as a bridge to orthotopic liver transplantation in terminal liver failure. Transplantation 1997: 63: 559-69.
  • Bilir B, Durham JD, Krystal J, et al. Transjugular intra-portal transplantation of cryopreserved human hepatocytes in a patient with acute liver failure. Hepatology 1996: 24 (Suppl): 308A.
  • Reyes J, Rubinstein WS, Mieles L, et al. The use of cultured hepatocyte infusion via the portal vein for the treatment of ornithine transcarbamoylase deficiency by transplantation of enzymatically competent ABO/Rh-matched cell. Hepatology 1996: 24(Suppl): 308A.
  • Raper SE, Grossman M, Rader DJ, et ill. Safety and feasibility of liver directed ex vivo gene therapy for homozygous familial hypercholesterolaemia. Ann Surg 1996:223: 116-26.
  • Fox IJ, Chowdhury JR, Kauffman SS, et al. Treatment of Crigler-Najjar syndrome Type I with hepatocyte transplantation. N Engl J Med 1998: 338: 1422-6.
  • Lake JR. Hepatocyte transplantation. N Engl J Med 1998: 338: 1463-4.
  • Petersen BE, Bowen WC, Patrene KD, et al. Bone marrow as a potential source of hepatic oval cells. Science 1999: 284: 1168-70.
  • Theise ND, Nimmakayalu M, Gardner R, et al. Liver from hone marrow in humans. Hepatology 2000: 32: 11- 16.
  • Lemmer ER, Krige JE, Hall P de Ia M, Bornman PC, Taylor EG, Terblanche J. Surgical resection for hepatocellularcarcinoma in Cape Town: a clinical and histopathological study. S Afr J Meet 1998: 88: 1575-80.
  • Peterson BE, Goff JP, Greenberger JS, Michalopoulos GK. Hepaticoval cells express the hematopoietic stem cell marker Thy-1 in the rat. Hepatology 1998: 27: 433-45.

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